Engineering ‘Smart Cells’ With Limitless Potential

Dr. Hana El-Samad builds new biological circuits in living cells using a revolutionary, lab-synthesized artificial protein she co-designed on a computer.

What drove Hana El-Samad, PhD, to embark on a quest to command a living cell by remote control? Curiosity. 

By engineering cells to receive and interpret light, she found she could control these cells and manipulate the expression of the genes within them. Her biological-signaling research, which looks at how cells use elaborate feedback mechanisms to autocorrect after disturbances, has been influenced by her background in electrical and mechanical engineering and has revolutionary implications for medicine. 

For instance, she is building customized guidance and feedback circuits from biological molecules and incorporating them into cells. With this technology, human cells could soon be programmed to fly through the body to deliver precise and smart therapies, much like therapeutic drones. 

Amazingly, this can be accomplished without any direct human intervention thanks to a first-of-its-kind artificial protein – designed on a computer and synthesized in the lab – that can be used to build brand-new biological circuits inside living cells. These circuits transform ordinary cells into smart cells that are endowed with remarkable abilities. 

This new protein, formally known as the Latching Orthogonal Cage-Key pRotein, or LOCKR, is described in a pair of papers published in the journal Nature. And it’s unlike anything biologists – or nature itself – has ever devised.  

“While many tools in the biotech arsenal employ naturally occurring molecules that were repurposed for use in the lab, LOCKR has no counterpart in nature,” said El-Samad, the Kuo Family Professor of Biochemistry and Biophysics at UCSF and co-senior author of the new studies. 

“LOCKR is a biotechnology that was conceived of and built by humans from start to finish. This provides an unprecedented level of control over the way the protein interacts with other components of the cell, and will allow us to begin tackling unsolved – and previously unsolvable – problems in biology, with important implications for medicine and industry.” 

El-Samad is just one of the hundreds of UCSF scientists whose work has taken flight thanks to funding from the Program for Breakthrough Biomedical Research. The program, which celebrated its 20th year in 2019, embodies a bold, risk-taking approach to scientific inquiry. 


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